1a: 1. The primary scientific goal of the research is to apply human genetics to the identification of new drug targets, the validation of existing targets and therapeutics, and the discovery of biomarkers that may correlate with treatment response or aid in stratifying patients and diseases at a genetic or molecular level. In addition to the direct benefit of advancing the development of new medicines and benefiting patients, this research will also accelerate our understanding of the role of genetics in human health and disease.

1b: The research project will generate sequencing data on up to 500,000 UK Biobank participants. This will be combined with phenotypic data that is available from UK Biobank participants, with the purpose of improving our understanding of the relationship between genetic variation and human traits. Such a resource will be one of the largest of its kind and will be made available to UK Biobank. It is anticipated that this resource will greatly facilitate research into the role of genetic variation in human health and disease and has the potential to make a significant impact on health-related research.

1c: The scope of the research program includes, (i) transfer of de-identified phenotypic data and genotype data to joint Applicants (RGC and GSK), (ii) transfer of biospecimens from UK Biobank to the Regeneron Genetics Center (RGC), (iii) whole exome sequencing of DNA samples by the RGC, (iv) transfer of genomic sequence data to GSK and UK Biobank by RGC and (v) analyses of the datasets in accordance with the goals, aims, and study designs described in this application by each of the Applicants (RGC and GSK), either jointly or independently.

1d: Under this research project, the Applicants endeavour to sequence DNA samples from all current UK Biobank participants (the full cohort of approximately 500,000 participants). The Applicants have established various project phases, in which they aim to sequence a certain number of samples per project phase. After completion of each project phase, the Applicants will determine whether they will proceed with the subsequent project phase.

Project extension February 2019:

We propose a specific addendum to cover investigation of the diversity of phenotype data (including the wearables data such as accelerometry), to investigate their association with disease phenotypes. Specifically, we aim to i) understand variability in the general population; ii) implement machine learning approaches to identify features associated with disease status or disease stratification. The only addition we seek is to be able to analyse the wearables data and investigate association with disease status or stratification. Thus, we now mention digital biomarkers specifically above. The scientific team suggested we submit this as a change request to explicitly mention digital biomarkers.